The objective of this proposal is to continue our current studies on the autonomic regulation of salivary secretory mechanisms. Two specific areas where the ANA may play a critical regulatory role are to be considered: 1) the coupling in the secretion of the aqueous (water and electrolytes) and the macromolecular fractions of saliva. 2) the coupling between the function of acini and ducts. A second objective is to develop models where the regulation of these two coupling mechanisms is disturbed. To accomplish these objectives we propose to compare the following aspects of the stimulus secretion coupling mechanisms in an isolated, perfused preparation of the submaxillary gland of normal rats and of rats chronically treated with catecholamine depleters and with receptor blocking agents: 1) the external requirements for the secretion of the two fractions of saliva; 2) the response to graded doses of specific secretatogues; 3) the number and characteristics of autonomic receptors; 4) the levels of glandular cyclic nucleotides; 5) the constancy of the primary secretion collection of micropuncture; 6) the volume and composition of final saliva; 7) the morphological changes accompanying secretion; 7) the nature and extent of ductal electrolyte transport. An in situ preparation for the microperfusion of the main excretory duct will also be used to study ductal transport. By comparing these morphological, metabolic and secretory indices in normal glands with those of drug treated animals we expect to improve our understanding of the salivary secretory mechanism and of factors of a regulatory nature that may disturb it in diseases such as cystic fibrosis.